scholarly journals Mycophenolate Improves Brain–Gut Axis Inducing Remodeling of Gut Microbiota in DOCA-Salt Hypertensive Rats

Antioxidants ◽  
2020 ◽  
Vol 9 (12) ◽  
pp. 1199
Author(s):  
Iñaki Robles-Vera ◽  
Néstor de la Visitación ◽  
Manuel Sánchez ◽  
Manuel Gómez-Guzmán ◽  
Rosario Jiménez ◽  
...  

Microbiota is involved in the host blood pressure (BP) regulation. The immunosuppressive drug mofetil mycophenolate (MMF) ameliorates hypertension. The present study analyzed whether MMF improves dysbiosis in mineralocorticoid-induced hypertension. Male Wistar rats were assigned to three groups: untreated (CTR), deoxycorticosterone acetate (DOCA)-salt, and DOCA treated with MMF for 4 weeks. MMF treatment reduced systolic BP, improved endothelial dysfunction, and reduced oxidative stress and inflammation in aorta. A clear separation in the gut bacterial community between CTR and DOCA groups was found, whereas the cluster belonging to DOCA-MMF group was found to be intermixed. No changes were found at the phylum level among all experimental groups. MMF restored the elevation in lactate-producing bacteria found in DOCA-salt joined to an increase in the acetate-producing bacteria. MMF restored the percentage of anaerobic bacteria in the DOCA-salt group to values similar to control rats. The improvement of gut dysbiosis was associated with an enhanced colonic integrity and a decreased sympathetic drive in the gut. MMF inhibited neuroinflammation in the paraventricular nuclei in the hypothalamus. This study demonstrates for the first time that MMF reduces gut dysbiosis in DOCA-salt hypertension models. This effect seems to be related to its capacity to improve gut integrity due to reduced sympathetic drive in the gut associated with reduced brain neuroinflammation.

2021 ◽  
Vol 18 (01) ◽  
pp. 1
Author(s):  
Yance Anas ◽  
Ika Nilam Cahyani ◽  
Ulum Firnanda Sukma

ABSTRACT Previous studies accomplished that the chayote ethanol extract (Sechium edule (Jack) Sw) had an antihypertensive effect. To get and identify the active compound, we fractionated the extract and evaluated its antihypertensive activity. This study aims to investigate the antihypertensive effect of the n-hexane fraction (HF-CEE) and ethyl acetate fraction of chayote ethanol extract (EAF-CEE) in monosodium glutamate (MSG)-induced hypertensive rats. We made the chayote extract using the maceration method by soaking the chayote simplicia in ethanol 70%. HF-CEE and EAF-CEE were obtained by stratified fractionation using n-hexane and ethyl acetate. An antihypertensive effect of the fraction measured on MSG-induced hypertension male Wistar rats after MSG 100 mg/kg BW/day (p.o) treatment for 14 days. The study concluded that HF-CEE and EAF-CEE had an antihypertensive effect in MSG-induced hypertensive rats. The EAF-CEE antihypertensive effect is higher than HF-CEE. Therefore, the FEAF-CEE active compounds need to be isolated, identified, developed, and their potential as an antihypertensive candidate. Keywords: Antihypertensive, chayote, ethyl-acetate fraction, Sechium edule, monosodium glutamate


1983 ◽  
Vol 61 (8) ◽  
pp. 888-892 ◽  
Author(s):  
Nguyen T. Buu ◽  
Otto Kuchel ◽  
Jacques Genest

The catecholamine concentrations in the urines and in the tissues of the kidney, heart, striatum, and hypothalamus of control rats and rats treated with deoxycorticosterone and salt for 2-week and 5-week periods were measured and compared. In 2-week-treated rats there were no changes in blood pressure and catecholamines. In 5-week-treated rats, the blood pressure increased from 117 ± 5 to 152 ± 5 mmHg (1 mmHg = 0.13 kPa) and there was an increase of urinary dopamine, norepinephrine, and epinephrine. The kidney and heart tissues of the hypertensive rats showed a decrease of norepinephrine while in the hypothalamus all three catecholamines were increased. These data suggest that dopamine and epinephrine may also be involved in the sympathetic dysfunction in deoxycorticosterone–salt hypertension. They demonstrate for the first time an increase of dopamine, norepinephrine, and epinephrine in the hypothalamus of deoxycorticosterone–salt hypertensive rats.


2008 ◽  
Vol 294 (1) ◽  
pp. F84-F92 ◽  
Author(s):  
Martha Franco ◽  
Rocio Bautista ◽  
Oscar Pérez-Méndez ◽  
Lidia González ◽  
Ursino Pacheco ◽  
...  

Since marked renal vasoconstriction is observed in angiotensin II (ANG II)-mediated hypertensive rats, we studied the possible interaction between ANG II and adenosine in this model. ANG II was infused into male Wistar rats through osmotic minipumps (435 ng·kg−1·min−1) for 14 days. In sham and ANG II groups, renal tissue and interstitial adenosine were measured; both increased to a similar twofold extent in the ANG II-treated rats (31.40 ± 4 vs. 62.0 ± 8.4 nM, sham vs. ANG II, interstitial adenosine; P< 0.001). The latter decreased by 47% with the specific blockade of 5′-nucleotidase. Glomerular hemodynamics demonstrated marked renal vasoconstriction in the angiotensin-treated group, which was reverted by an adenosine A1-receptor antagonist (8-cyclopentyl-1,3-dipropylxanthine, 10 μg·kg−1·min−1). 5′-Nucleotidase and adenosine deaminase (ADA) activities were measured in the cytosolic and membrane fractions. Only the membrane ADA activity decreased from 1,202 ± 80 to 900 ± 50 mU/mg protein in the ANG II-treated rats ( P< 0.05), as well as in their protein and mRNA expression. Despite the adenosine elevation, A1 and A2b receptor protein did not change; in contrast, downregulation was observed in A2a receptor and upregulation in A3 receptor. A similar pattern was found in the cortex and in the medulla; mRNA significantly decreased only in the A3 receptor in both segments. These results suggest that the elevation of renal tissue and interstitial adenosine contributes to the renal vasoconstriction observed in the ANG II-induced hypertension and that it is mediated by a decrease in the activity and expression of ADA, increased production of adenosine, and an induced imbalance in adenosine receptors.


2011 ◽  
Vol 26 (suppl 1) ◽  
pp. 57-59 ◽  
Author(s):  
Marcio Wilker Soares Campelo ◽  
Ana Paula Bomfim Soares Campelo ◽  
Luiz Gonzaga de França Lopes ◽  
Armenio Aguiar dos Santos ◽  
Sergio Botelho Guimarães ◽  
...  

PURPOSE: To evaluate the effect of Rut-bpy (Cis-[Ru(bpy)2(SO3)(NO)]PF 6), a novel nitric oxide donor in Nω-nitro-L-arginine methyl ester (L-NAME)-induced hypertensive rats. METHODS: Twenty-four male Wistar rats were randomly assigned to four groups (n=6), named according to the treatment applied (G1-Saline, G2-Rut-bpy, G3-L-NAME and G4-L-NAME+Rut-bpy). L-NAME (30 mg/Kg) was injected intraperitoneally 30 minutes before the administration of Rut-bpy (100 mg/Kg). Mean abdominal aorta arterial blood pressure (MAP) was continuously monitored. RESULTS: Mean arterial blood pressure (MAP) in G3 rats rose progressively, reaching 147±16 mmHg compared with 100±19 mm Hg in G1 rats (p<0.05). In G4 rats, treated with L-NAME+Rut-bpy, MAP reached 149+11 mm Hg while in G2 rats, treated with Rut-bpy, MAP values were 106±11 mm Hg. In G1 rats these values decreased progressively reaching 87+14 mm Hg after 30 minutes. An important finding was the maintenance of the MAP throughout the experiment in G2 rats. CONCLUSION: Rut-bpy does not decrease the MAP in L-Name induced hypertensive rats. However, when it is used in anesthetized hypotensive rats a stable blood pressure is obtained.


1994 ◽  
Vol 267 (6) ◽  
pp. E927-E933 ◽  
Author(s):  
D. T. Van den Berg ◽  
E. R. de Kloet ◽  
W. de Jong

The role of brain mineralocorticoid receptor (MR) sites in the pathogenesis of mineralocorticoid hypertension was studied after an intracerebroventricular injection of the MR antagonist RU-28318. Male Wistar rats received subcutaneously implanted deoxycorticosterone acetate (DOCA) pellets and were maintained on 0.9% saline as drinking solution. Under these conditions hypertension developed in approximately 5 wk as assessed in conscious rats by means of the tail-cuff technique. During the development of this hypertension (after 3 wk of DOCA-salt treatment) a single intracerebroventricular injection of the specific MR antagonist RU-28318 reduced systolic blood pressure (SBP) as measured with the tail-cuff method. A decrease in SBP was observed 2–24 h after this intracerebroventricular injection, with the lowest SBP values occurring at 8 h. In these animals (3 wk after DOCA implantation) continuous direct blood pressure recording via chronic cannulation revealed, on the day of the intracerebroventricular injection of RU-28318, a slight increase in arterial pressure during the light phase, followed by a decrease during the dark phase. In the established hypertensive rats (5 wk after DOCA RU-28318 on the arterial pressure or heart rate was detectable. It is concluded that central MR blockade during the development of the DOCA-salt hypertension reduces blood pressure within 24 h assessed with 1) the indirect method at certain time points after exposure to warming and stress and 2) the direct method during the dark phase of the diurnal cycle.


1981 ◽  
Vol 61 (s7) ◽  
pp. 53s-55s ◽  
Author(s):  
Atsuo Goto ◽  
Toshio Ikeda ◽  
Louis Tobian ◽  
Junichi Iwai ◽  
Mary A. Johnson

1. The rise in blood pressure in Dahl salt-sensitive rats that received intracerebroventricular 6-hydroxydopamine was almost half that of the control rats throughout 20 weeks of high (8%) NaCl feeding. 2. The rise in bood pressure in Dahl salt-sensitive rats with bilateral complete electrolytic lesions of the paraventricular nuclei was almost half that of the control rats during 12 weeks of high (8%) NaCl feeding. 3. The bilateral complete electrolytic lesions of the suprachiasmatic nuclei enhanced the development of NaCl hypertension in Dahl salt-sensitive rats. 4. These results show that NaCl-induced hypertension in Dahl salt-sensitive rats requires the integrity of the central nervous system catecholaminergic neurones and the paraventricular nuclei for its full expression.


1991 ◽  
Vol 65 (04) ◽  
pp. 411-414 ◽  
Author(s):  
Keizo Umegaki ◽  
Hiromi Saegusa ◽  
Masato Kurokawa ◽  
Tomio Ichikawa

SummaryEffects of vitamin E on platelet function and serum lipid peroxide levels were investigated in DOCA-salt hypertensive rats. In the hypertensive rats, ADP- and collagen-induced platelet aggregation in whole blood were markedly attenuated and accompanied by a reduction of serotonin content as compared with the normotensive controls. These facts indicated the appearance of exhausted platelets, which have already been activated in vivo, due to the hypertension. Platelet vitamin E levels were decreased by 50%, while serum lipid peroxide levels were increased 3.6-fold in the hypertensive rats. Vitamin E administration (10 times the dietary intake) during the experimental periods did not influence either the aggregability or the serotonin content of platelets from the hypertensive rats. However, vitamin E administration significantly prevented the elevation of serum tipid peroxides due to the hypertension. These results suggest that vitamin E administration has little effect on platelet activation in vivo due to DOCA-salt hypertension.


2019 ◽  
Vol 20 (4) ◽  
pp. 302-308 ◽  
Author(s):  
Carla R.F. Volobuff ◽  
Pedro C.O. Junior ◽  
Sidney M. dos Santos ◽  
Zefa V. Pereira ◽  
Diego C. Ferreira ◽  
...  

Background: The genus Psychotria and Palicourea are reported as a source of alkaloids and iridoids, which exhibit biological activities. This study aimed to evaluate antiproliferative and anticholinesterase activities and quantification of the alkaloids of seven species among the genus found in Mato Grosso do Sul region in Brazil. Methods: Concentrations of alkaloids were measured spectrophotometrically. The extracts were submitted to antiproliferative activity against ten cell lines. The anticholinesterase activity of the extracts was developed using brain structures of male Wistar rats: cerebral cortex, hippocampus, hypothalamus and striatum by the Ellman method. Results: Alkaloids from Psychotria and Palicourea species were quantified which showed values of 47.6 to 21.9 µg/g. Regarding the antiproliferative potential, Palicourea crocea demonstrated selectivity against the 786-0 cell line (GI50: 22.87 µg/mL). Psychotria leiocarpa inhibited cell growth against OVCAR-3 (GI50: 3.28 µg/mL), K-562 (GI50: 5.26 µg/mL), HaCaT (GI50: 27.20 µg/mL), PC-3 (GI50: 34.92 µg/mL), MCF-7 (GI50: 35.80 µg/mL) and P. capillacea showed activity against OVCAR-3 (GI50: 2.33 µg/ml) and U251 (GI50: 16.66 µg/ml). The effect of acetylcholinesterase inhibition was more effective in the hippocampus, demonstrating inhibition for Paliourea crocea, Psychotria deflexa, P. brachybotrya and P. leiocarpa of 70%, 57%, 50% and 40%, respectively, followed by P. poeppigiana and P. capillacea, inhibiting 21%, compared to the control. Conclusion: Herein, the present work showed for the first time, anticholinesterasic and antiproliferative activities of extracts of Palicourea and Psychotria seem to be mainly associated with the levels of alkaloids in the leaves of these species.


1983 ◽  
Vol 245 (6) ◽  
pp. F755-F762 ◽  
Author(s):  
B. M. Iversen ◽  
L. Morkrid ◽  
J. Ofstad

The afferent arteriolar diameter (dAA) was investigated during development of hypertensive renal disease in normal and uninephrectomized control rats, in chronic DOCA-salt (DOCA), post-DOCA (p-DOCA), and chronic two-kidney one-clip (2K-1C) hypertensive rats, and in post-two-kidney one-clip (p-2K-1C) normotensive rats. dAA was measured by the microsphere method. Nephron loss was present in the kidneys exposed to elevate blood pressure. The dAA was reduced from 19.9 to 17.2 micron in the DOCA group (P less than 0.001) and from 19.1 to 16.3 micron in the nonclipped kidneys in the 2K-1C group (P less than 0.001). The dAA increased from 19.9 to 20.7 micron in the p-DOCA group. Afferent arteriolar dilatation from 19.1 to 21.0 micron (P less than 0.001) was present about 50 days after clipping in the 2K-1C group; in the clipped kidneys the dAA returned to normal (18.9 micron) after declipping. No relation between the dAA and plasma renin concentration was observed. In all models dAA was the same in three cortical layers of equal thickness. Accordingly, chronic renal DOCA-salt hypertension constricts the afferent arteriole with angiotensin-independent mechanisms. Autoregulatory dilatation of the afferent arteriole seems to be maintained for at least 50 days. When the hypertension is moderate, dAA in damaged kidneys may be dilated.


1999 ◽  
Vol 277 (1) ◽  
pp. H399-H404 ◽  
Author(s):  
Pilar Nava ◽  
Verónica Guarner ◽  
Rosalinda Posadas ◽  
Israel Pérez ◽  
Guadalupe Baños

Insulin-elicited endothelin release in hypertriglyceridemic, hypertensive, hyperinsulinemic (HTG) rats was shown. Weanling male Wistar rats were given 30% sucrose in their drinking water for 20–24 wk. In vitro contractions of aorta and femoral arteries were elicited with 40 mM KCl. Endothelin release induced with KCl plus 50 μU/ml insulin resulted in increases in contractile responses: 41 ± 5.9 and 57 ± 6% for control and 65.5 ± 6 and 95 ± 9% for HTG aortas and femoral arteries, respectively. The endothelin ETB-receptor blocker BQ-788 decreased responses to KCl + insulin by 39 ± 8 and 53 ± 5% in control and 48 ± 13 and 79 ± 3.5% in HTG aortas and femoral arteries, respectively. The ETA-receptor antagonist PD-151242 inhibited these responses by 12 ± 10 and 1 ± 9% in control and by 51.5 ± 9 and 58.5 ± 1% in HTG aortas and femoral arteries, respectively. These results suggest that endothelin may contribute to the hypertension in this model.


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